The synthesis and role of taurine in the Japanese eel testis

In teleost fish, the progestin 17α, 20β-dihydroxy-4-pregnen-3-one (DHP) is an essential component of the spermatogenesis pathway. In a series of investigations on the mechanisms underlying progestin-stimulated spermatogenesis, we have found that DHP up-regulates the expression of cysteine dioxygenase1 (CDO1) in the Japanese eel testis. CDO1 is one of the enzymes involved in the taurine biosynthesis pathway. To evaluate whether taurine is synthesized in the eel testis, cysteine sulfinate decarboxylase (CSD), another enzyme involved in taurine synthesis, was isolated from this species. RT-PCR and in vitro eel testicular culture revealed that although CSD was also expressed in eel testis, neither DHP nor other sex steroids affect CSD mRNA expression in a similar manner to CDO1. Using an in vitro eel testicular culture system, we further investigated the effects of DHP on taurine synthesis in the eel testis. HPLC analysis showed that DHP treatment significantly increases the taurine levels in the eel testis. These results suggest that DHP promotes taurine synthesis via the up-regulation of CDO1 mRNA expression during eel spermatogenesis. Furthermore, we observed from our analysis that although taurine does not induce complete spermatogenesis, it promotes spermatogonial DNA synthesis and the expression of Spo11, a meiosis-specific marker. These data thus suggest that taurine augments the effects of sex steroids in the promotion of spermatogonial proliferation and/or meiosis and hence that taurine plays important roles in spermatogenesis.     

Catabolism of taurine in Pseudomonas aeruginosa.

Cell-free extracts of taurine-grown Pseudomonas aeruginosa catalyze the transamination of taurine and pyruvate resulting in the formation of L-alanine and sulfoacetaldehyde. The enzyme responsible for this activity has been partially purified in order to demonstrate its participation in a pathway of taurine degradation. Ethyl methane sulfonate treatment of Ps. aeruginosa yielded a mutant deficient in taurine transaminase and incapable of growing on taurine indicating that the enzyme is of physiological significance in this organism.     

Hypolipidemic action of taurine in rats.

The effect of taurine on the serum and liver cholesterol and triglyceride levels was studied in rats fed cholesterol plus cholic acid. Four groups of 4 weeks old rats were fed control diet, hypercholesterolemic diet (HCD), HCD + 1% taurine or HCD + 2% taurine for 8 weeks. Addition of taurine in HCD diet showed a significant reduction not only in serum total cholesterol and triglyceride levels but also in liver total cholesterol, lipid and triglyceride contents compared to the animals fed HCD alone. Histological examination of organs of these animals showed severe fatty vacuolation in livers and signet ring type vacuolation in kidneys of rats fed HCD. Taurine showed ameliorating effect on these abnormalities. The animals fed taurine in HCD also showed increased bile and sterol excretion in faeces compared to rats fed HCD alone. Taurine showed significant hypocholesterolemia in rats probably by enhancing the catabolism of cholesterol and reducing the absorption of dietary cholesterol.     

Effects of taurine in glucose and taurine administration

Summary. Taurine has several biological processes such as hypoglycemic action, antioxidation, detoxification, etc. To assess the effect of taurine administration on the guinea pigs with hyperglycemia, blood glucose, C-peptide levels together with morphologic alterations in the pancreatic ultrastructure were investigated in terms of hypoglycemic action and malondialdehyde and total sulfhydryl group levels with regard to oxidation-antioxidation relation. Animals were divided into four groups of six. Glucose supplementation group was administrated a single dose of glucose (400mg/kg, i.p.) injection. Glucose and taurine supplementation group was administrated glucose treatment (a single dose, 400mg/kg, i.p.) following taurine (a single dose, 200mg/kg, i.p.). Taurine and glucose supplementation group was administered taurine treatment (a single dose, 200mg/kg, i.p.) following glucose treatment (a single dose, 400mg/kg, i.p.). Control animals received no treatment. Blood samples were collected at the end of the experiments for the determination of glucose, C-peptide (indicator of insulin secretion), lipid peroxidation (thiobarbituric acid reactive substances), and total sulfhydryl groups levels. Pancreatic tissue samples were then collected and processed for transmission electron microscopy. The findings showed that glucose supplementation following taurine administration significantly decreased blood glucose level by increasing C-peptide level and the pancreatic secretion stimulated morphologically and insignificantly changed thiobarbituric acid reactive substances and total sulfhydryl group levels. These observations suggest that taurine administration may be useful in hyperglycemia because of its hypoglycemic and protective effects.     

Coenzyme A derivatives of bile acids-chemical synthesis, purification, and utilization in enzymic preparation of taurine conjugates.

Synthesis of the coenzyme A derivatives of bile acids by the mixed anyhydride method results in a product that is contaminated by unreacted CoASH and bile acid. These compounds can be purified by Sephadex LH-20 chromatography. In each case, the purified product is free of starting materials and exhibits an equimolar ratio of bile acid, coenzyme A, and thioester bond. Millimolar extinction coefficients were calculated for these compounds as A259 nm, 15.03 +/- 0.58; A232 nm, 7.60 +/- 0.17; and A232 nm for the thioester bond, 4.12 +/- 0.17. These CoA derivatives were hydrolyzed in strongly alkaline solution, but were stable at physiologic temperature and pH. Utilization of these compounds in the enzymic preparation of taurine conjugates of bile acids indicated 94% activity. These purified CoA derivatives may be useful in studying the enzymic conjugation of bile acids.     

Physical and structural properties of taurine and taurine analogues

Summary In a variety of mammalian species it has been established that taurine is a necessary component of the visual system, however, the exact mechanism(s) as to the function of taurine is(are) elusive. Additionally, taurine is speculated to be a membrane stabilizer by interacting with phospholipids and a regulator of protein phosphorylation. Therefore the inhibition by taurine and taurine analogues of the phosphorylation of an 20 kDa protein present in the mitochondrial fraction of the rat retina has been investigated using computational methods. Correlations between molecular weight, molecular volume, and calculated pKa values vs. IC₅₀ values are reported. These data appear to support the hypotheses according to Lombardini and Props that the inhibition of the phosphorylation of an 20kDa protein by taurine and taurine analogues is dependent on (i) the critical distance between the nitrogen and sulfur atoms in the taurine moiety (S-C-C-N) of the analogue; (ii) the environment of the nitrogen atom in the taurine analogue (saturated ring vs. unsaturated ring); and (iii) the placement of both the sulfur and nitrogen atoms not being present simultaneously in the ring structure. Using computational methods we present results that support hypotheses (i) and (ii).     

Response of the kitten to dietary taurine depletion: effects on renal reabsorption, bile acid conjugation and activities of enzymes involved in taurine synthesis

Kittens were adapted to a semipurified diet and then fed either a control diet that contained 0.1% taurine or a taurine-free diet for 6 weeks; at the end of the feeding period, kittens fed the taurine-free diet had plasma and liver taurine concentrations that were 0.38 and 0.15%, respectively, of those for control kittens. Hepatic cysteinesulfinate decarboxylase activity in taurine-deficient kittens was five-times the level in control kittens, but hepatic cysteine dioxygenase activity was not affected by the dietary treatment. Taurine-conjugated bile acids made up 98% of the total bile acids in the gall bladder of control kittens, but they accounted for only 44% of the total bile acids in the bile of taurine-depleted kittens; both the concentrations of taurine-conjugated bile acids and total bile acids were markedly decreased in taurine-deficient kittens. No effect of taurine depletion on the fractional excretion of taurine in the urine was observed. The kitten may have some mechanisms for adapting to a low-taurine diet, but these are clearly not sufficient to maintain tissue taurine levels in the absence of dietary taurine.     

Net taurine transport and its inhibition by a taurine antagonist

P₂-fractions were isolated from rat brain, and used to study net taurine transport. The fractions were incubated in increasing concentrations of [³H]taurine and the intraterminal concentration measured by liquid scintillation and amino acid analysis. The membrane potential of the isolated fractions was estimated using⁸⁶Rb⁺ as a marker for intracellular K⁺. Taurine was synthesized in the P₂-fraction when incubated in taurine free medium. At external taurine concentrations below 370 M a significant amount of the endogenous taurine was released to the incubation medium. Net taurine uptake into the P₂-fraction was achieved at external taurine concentrations exceeding 370 M. The taurine antagonist 6-aminomethyl-3-methyl-4H, 1, 2, 4-benzothiadiazine-1, 1-dioxide (TAG) competitively inhibited taurine and [³H]taurine transport into the P₂-fraction. As the external concentration of taurine was increased, the accumulation of⁸⁶Rb⁺ into the P₂-fraction was facilitated. This indicated an increasing hyperpolarization of the neuronal membrane as taurine transport shifted from release towards uptake. TAG reduced the hyperpolarization that paralleled taurine accumulation, in a dose dependent manner. Our results indicate that relatively low transmembranal gradients of taurine may be maintained by an electrogenic taurine transporter having a large transport capacity. Such a transporter may well serve the needs of osmotic regulation, i.e. to transport large amounts of taurine in any direction across the neuronal membrane.     

Formation of taurine and amino acid pools in rat tissues upon stimulation of NAD synthesis

A single intraperitoneal injection of nicotinamide (500 mg/kg) to mongrel albino rats causes a 6-hour increase in the 2-oxoglutarate level and the free NAD+/NADH ratio in liver mitochondria. The levels of taurine and taurocholates as well the activity of cysteine oxidase in liver tissues remains thereby unchanged, whereas the cysteine transaminase activity diminishes. In the heart and brain of experimental animals the activity of both enzymes is decreased. In the liver, blood plasma and heart of experimental animals, the Ala and Ser levels are low, whereas the taurine content is elevated both in blood plasma and brain. Nicotinamide administration eliminates positive correlations between the levels of taurine, its precursors and metabolically bound amino acids. In the liver the negative correlations between the activities of cysteine oxidase and cysteine transaminase observed in the control group disappear in the experimental group. Apparently, one of regulatory mechanisms of the taurine pool formation in the liver is the ratio of activities of the both enzymes as well as their competition at the substrate level. This emphasizes the importance of the transamination reactions in the metabolism of sulphur-containing amino acids.     

Oxidation of hypotaurine to taurine by ultraviolet irradiation.

Oxidation of hypotaurine to taurine is known to occur in vivo. Search for an enzyme performing that oxidation has been unsuccessful. However, fast and quantitative oxidation of hypotaurine (and other sulfinates) by ultraviolet irradiation has now been observed. The reaction is first order and pH-dependent, and its rate depends strongly on the kind of sulfinate irradiated. Only the corresponding sulfonate is recovered as the product under the relatively mild conditions used. Catalase or superoxide dismutase does not affect the oxidation, which is oxygen-dependent. A simple reaction scheme is proposed to account for the findings.     

Brain protein synthesis rates are not sensitive to elevated GABA,taurine, or glycine

The effects of elevated levels of GABA, glycine, or taurine on the rate of protein synthesis in plasma, brain, liver, and muscle of adult mice were measured in in vivo experiments after a flooding dose of labeled valine. Elevation of these amino acids caused hypothermia; keeping the animals in an incubator maintained physiological body temperature. The increase in GABA or glycine did not affect the rate of protein synthesis in these tissues to a significant degree. The increase in taurine levels caused inhibition of valine incorporation in plasma, liver, and muscle, while brain protein synthesis was unaffected. When glycine was increased in brain, the uptake of labeled free valine in the brain was greater.